Is DBR1 p.Arg25Trp (c.73C>T) pathogenic?

DBR1 p.Arg25Trp (c.73C>T) is classified Conflicting classifications of pathogenicity in DBR1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-24). AlphaMissense: likely benign (0.229); Rare (popmax 0.233%, sas).

How common is DBR1 p.Arg25Trp (c.73C>T) in the general population?

DBR1 p.Arg25Trp (c.73C>T) is rare (popmax 0.233%, sas) (gnomAD).

What do computational predictors say about DBR1 p.Arg25Trp (c.73C>T)?

AlphaMissense predicts likely benign (score 0.229) — an in-silico prediction, not a clinical call.

DBR1 p.Arg25Trp

c.73C>T · rs540723626 · VCV1937607

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.229 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.233%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.229	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -12.57	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 12 kb · p 0.4 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.233% South Asian · 212/90,922 alleles

Filtering AF 0.207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.197%

Overall 0.0138% 223/1,612,632 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.233%	429
Remaining individualsnot grpmax-eligible	0.0144%	6,931
East Asian	0.00223%	44,866
European (non-Finnish)	8.48e-05%	1,179,645

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DBR1
Protein: p.Arg25Trp
Coding: c.73C>T
MANE Select: NM_016216
dbSNP: rs540723626
Type: single nucleotide variant
Location: chr3:138174723 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.04

Full DBR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DBR1 c.489+5G>A Uncertain significance ★★ same type
DBR1 p.Ala233Thr Uncertain significance ★★ ⚠ same type
DBR1 p.Ala443Thr Uncertain significance ★★ ⚠ same type
DBR1 p.Ala458Asp Uncertain significance ★★ ⚠ same type
DBR1 p.Arg197Gln Uncertain significance ★★ ⚠ same type
DBR1 p.Arg197Ter Uncertain significance ★★ same type
DBR1 p.Arg527Ser Uncertain significance ★★ ⚠ same type
DBR1 p.Asn405His Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dbr1-p-arg25trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown